Bubble-Transcranial Doppler Detects PFOs in Elderly With Cryptogenic TIA

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The use of bubble-TCD was deemed feasible in approximately 91% of patients included in the cohort.
The use of bubble-TCD was deemed feasible in approximately 91% of patients included in the cohort.

Contrast-enhanced transcranial Doppler (bubble-TCD) sonography is a useful noninvasive bedside technique for detecting probable patent foramen ovale (PFO) among elderly patients with transient ischemic attack (TIA) or nondisabling stroke, according to study findings published in Lancet Neurology.

Additionally, researchers found that right-to-left shunt (RLS) was associated with an increased risk for cryptogenic events or for ischemic events where no clear cause can be found in elderly patients.

A total of 572 consecutive patients living in the United Kingdom (mean age 70.0 years [standard deviation, 13.7]) with TIA or nondisabling stroke who attended a TIA and stroke clinic or had 1-month follow-up data from a stroke clinic were enrolled.

In the instance when ischemic events demonstrated no clear cause following assessment by brain imaging, electrocardiogram, complete vascular imaging, or transthoracic echocardiography, the event was categorized as cryptogenic. Cardioembolic, small vessel disease, large artery disease, events of other cause, or events of multiple causes were labeled as having a known cause.

Bubble-TCD sonography was performed by operators masked to participants' presentation. The researchers also performed a systematic review and meta-analysis of studies that included data on age-specific PFO prevalence in cryptogenic stroke and strokes of known cause.

The use of bubble-TCD was deemed feasible in approximately 91% (n=523) of patients included in the cohort. Of these, a total of 397 patients were >60 years of age. The prevalence of RLS was significantly higher among patients with cryptogenic events vs participants with cerebrovascular events of known cause (odds ratio [OR], 1.93; 95% CI 1.32-2.82; P =.001). Cryptogenic events were also higher among patients >60 years of age (OR, 2.06; 95% CI, 1.32-3.23; P =.001).

Study investigators pooled data from the main cohort with those of 2 previously published studies of bubble-TCD, placing a specific focus on patients age >50 years. In this pooled analysis, there was a significant association between RLS and cryptogenic cerebrovascular events (OR, 2.35; 95% CI, 1.42-3.90; P =.0009).

Among the 41 patients in the main study with large RLS and TIA or nondisabling stroke of unknown cause, approximately 61% (n=25) were >60 years of age. According to the researchers, this translates to approximately 5951 patients who experience cryptogenic TIA or stroke per year in the United Kingdom.

Limitations of the analysis include its lack of generalizability across patient groups of other geographic regions as well as the lack of data on whether interatrial septal aneurysm was present in the cohort.

The results from this study suggest “age restrictions on access to diagnostic or therapeutic procedures in older patients with cryptogenic TIA or stroke should not prevent the necessary further research and randomized trials of PFO closure at older ages.”


Mazzucco S, Li L, Binney L, Rothwell PM; for the Oxford Vascular Study Phenotyped Cohort. Prevalence of patent foramen ovale in cryptogenic transient ischaemic attack and non-disabling stroke at older ages: a population-based study, systematic review, and meta-analysis. Lancet Neurol. 2018;17(7):609-617.

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